Herpes simplex virus-2 (HSV-2) and cytomegalovirus (CMV) infection can produce either overt or sub-clinical disease and both viruses can establish latent infections. It has been shown that infection of cells in culture by either inactivated HSV-2 or CMV can result in the outgrowth of cells with a transformed phenotype. This proposal is for a quantitative study of transformation in vitro by these herpesviruses using virions, UV-inactivated virus and sub-genomic fragments of viral DNA. The in vitro and in vivo characteristics of cell lines derived from the quantitatie studies will be examined. Investigation of the arrangement of retained viral sequences will be carried out using somatic cell genetic and biochemical methods. In situ hybridization, immunofluorescence for viral proteins, Southern blotting, reassociation kinetics, cytogenetic analysis and the use of cloned viral fragments are available methods. The in situ cytological hybridization approach to the detection of viral sequences will be developed, with particular reference to cervical neoplasia, by carrying out hybridization to specimens taken for histological diagnosis. These experiments will contribute towards an understanding of the putative role of HSV-2 in cervical carcinoma.